Recent high-throughput transcriptomic analyses have revealed that eukaryotic genomes transcribe up to 90% of the genomic DNA. (The ENCODE Project Consortium. The ENCODE (ENCyclopedia of DNA Elements) Project. Science 2004; 306:636-640). Only 1-2% of these transcripts encode for proteins, whereas the vast majority are transcribed as non-coding RNAs (ncRNAs).
The majority of the non-protein-coding transcripts belong to the group of lncRNAs, which are considered as >200 nucleotides in length. Most lncRNAs are characterized by nuclear localization, low expression, low level of sequence conservation and are composed of both poly A+ and poly A− transcripts, (Kapranov P, et al., “RNA maps reveal new RNA classes and a possible function for pervasive transcription.” Science 2007316:1484-1488) (Wu Q, et al., “Poly A− transcripts expressed in HeLa cells,” PLoS One 2008; 3:02803).
One subgroup of lncRNAs, termed large intergenic non-coding RNAs (lincRNAs), was described based on distinctive chromatin signature that marks actively transcribed genes. (Khalil A M et al., “Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression.” Proc Natl Acad Sci USA 2009; 106:11667-11672) (Guttman M et al., “Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals.” Nature 2009; 458:223-227). LincRNAs are marked by trimethylation of lysine 4 of histone H3 (H3K4me3) at their promoter and trimethylation of lysine 36 of histone H3 (H3K36me3) along the transcribed region.
Another subgroup of lncRNAs, termed enhancer RNAs (eRNAs), was recently reported to be transcribed from genomic enhancer regions. (Kim T K et al., “Widespread transcription at neuronal activity-regulated enhancers.” Nature 2010; 465:182-187) (De Santa F et al., “A large fraction of extragenic RNA pot II transcription sites overlap enhancers,” PLoS Biol 2010; 8:e1000384). Distinct from eRNAs, another subgroup of lncRNAs, termed ncRNA-activators (ncRNA-a) was classified as mono-directional, polyadenylated, and having a H3K4 trimethylation chromatin signature. (Orom U A, Derrien T, Beringer M, Gumireddy K, Giardini A, Bussotti G et al. Long noncoding RNAs with enhancer-like function in human cells. Cell 2010; 143:46-58.)